The emergence of drug-resistant pathogens is a growing threat to the healthcare system. Not only are current antibiotics becoming less effective, large pharmaceutical companies are shifting focus from new antimicrobial development to more lucrative drug discovery programs such as cancer therapeutics. Although it is recognized that “superbugs” are a major concern, the current market for new anti-infective drugs is relatively small in comparison to their significant regulatory and development costs.
The CDC has recently warned of the emergence of carbapenem-resistant Enterobacteriacea (CRE). The mortality rate for CRE bacteremia can be as high as 50%. Resistance of CREs to even the strongest available antibiotics leaves clinicians with few treatment options. The incidence of hospital-acquired CRE infections has increased from just over 1% ten years ago, to 4% today. Although CRE bacteremias are generally nosocomial infections, there is concern that the incidence of community acquired CRE could increase. Currently, the only strategy to combat the spread of CRE infections is through programs that educate healthcare professionals about prevention.
The conventional strategy for combating bacterial infections is to develop active drugs that specifically kill bacteria while avoiding damage to host tissue. This is a major challenge as some of the more potent antibiotics available today are quite toxic. For example, vancomycin is nephrotoxic, and may soon be contraindicated for patients undergoing extracorporeal oxygenation. Even if new antibiotics are successfully developed to address current drug resistance, new superbugs' will still emerge. Clearly, new strategies for combating infection, beyond drug discovery, are required.
Bloodstream infection, or bacteremia, is a major challenge in the ICU. Bacteremia can quickly lead to septic shock, meningitis, endocarditis, osteomyelitis and other metastatic complications. Staphylococcus aureus, Pseudomonas aeruginosa and Enterobacteriacea are the most common bacteria responsible for bacteremia or nosocomial infections. Severity of outcome for bacteremic patients is correlated to both the bacterial load and duration of bacteremia. A quantitative rt-PCR study of E. coli and S. aureus bacteremia patients showed that when the number of rDNA increased over 1238 copies/ml, mortality increased from 14.3% to 42.9% and septic shock increased from 31.4% to 85.7%. (see, “Quantitative rt-PCR Holds Promise as a Screening Tool for Patients with Severe Sepsis.” Kirkbright. 2011, Emergence Medicine Australasia, Vol. 23, p. 502). It was also found that a high blood concentration of N. meningitides is correlated with prolonged hospitalization, limb or tissue loss, need for dialysis, and mortality. (see, Severity of Meningococcal Disease Associated with Genomic Bacterial Load. Darton. 2009, Clinical Infectious Disease, Vol. 48, pp. 587-84). Likewise, another study showed that the severity of Pneumococcal pneumonia correlated with bacterial load in the blood: the mortality for patients with over 1000 S. pneumoniae DNA copies/ml of blood was 25.9% vs. 6.1% for patients exhibiting less than 1000 copies/ml. (see, Rell et al. “Severity of Pneumococcal Pneumonia Associated with Genomic Bacterial Load.” 2009, Chest, Vol. 136, pp. 832-840). In yet another study, a follow-up positive blood culture between 48 and 96 hours after initial diagnosis was shown to be the strongest predictor of complicated S. aureus bacteremia. Fowler. (see, “Clinical Identifiers of Complicated Staphylococcus aureus Bacteremia.” 2003, Arch Intern Med, pp. 2066-2072). Compounding the difficulty of effective bacteremia treatment is the often delayed administration of appropriate antibiotic therapy. It had been reported that for each hour of delay in treatment the mortality risk increases over 7%. (see Kumar et al., “Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock.” 6, 2006, Crit Care Med, Vol. 34, pp. 1589-96). A safe, broad-spectrum technology that could quickly reduce the bacterial load, and shorten the duration of bacteremia, would be a major breakthrough, since it could even be used without first identifying the type of bacteria present in the blood.
Although an adsorption hemoperfusion device with only heparinized media is already ‘broad-spectrum’, with the ability to target many high-profile bacteria responsible for nosocomial infections and bacteremia, gram negative bacteria such as E. coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa have a comparatively low affinity to heparin/HS.
In view of the foregoing, what is needed in the art are new methods and devices to remove bacteria and pathogens from blood. The present invention satisfies these and other needs.